In vitro and in vivo evaluation of mefenamic acid and its complexes with β-Cyclodextrin and HP-β-Cyclodextrin

Deelip V Derle, Mrudula Bele, Nikhil Kasliwal

Abstract


The objective of this research was to improve solubility, dissolution, and, consequently, bioavailability of mefenamic acid, a poorly water-soluble nonsteroidal anti-inflammatory drug, by complexation with β-Cyclodextrin and
HP-β-Cyclodextrin. The complexes of mefenamic acid with β-Cyclodextrin and HP-β-Cyclodextrin were prepared by kneading method and were characterized and evaluated to study the effect of complexation on dissolution profiles and
in vivo advantage. The complexes were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry studies. Phase solubility studies indicated complex formation with possible stoichiometry of 1:1 and a stability constant of 176 M-1 for β-Cyclodextrin and 103.8 M-1 for HP-β-Cyclodextrin. The characterization studies confirmed the inclusion of mefenamic acid within the nonpolar cavity of β-Cyclodextrin and of HP-β-Cyclodextrin. Remarkable improvement was observed in the in vitro drug release profiles in 0.1-N HCl and pH-6.8 phosphate buffer with
all complexes. Mefenamic acid also showed improvement in the in vivo activity when administered orally to rats as compared
with mefenamic acid per se.


Full Text:

PDF

References


Duchene D, Wouessidjewe D. Pharmaceutical uses of cyclodextrins and

derivatives. Drug Dev Ind Pharm 1990;16:2487-99.

Bekers O, Uijtendaal E, Beijnen J, Bult A, Underberg W. Cyclodextrins

in the pharmaceutical field. Drug Dev Ind Pharm 1991;17:1503-49.

Duchene D, Vaution D, Glomot F. Cyclodextrins their value in

pharmaceutical technology, Drug Dev Ind Pharm 1986;12:2193-215.

Menard F, Dedhiya MG. Physicochemical aspects of the complexation of

some drug with cyclodextrins. Drug Dev Ind Pharm 1990;16:91-113.

Aithal K, Udupa N, Sreenivasan K. Physicochemical properties of drug-

cyclodextrin complexes. Indian Drugs 1995;32:293-305.

Sanghavi N, Choudhary K, Matharu R, Viswanathan L. Inclusion

complexation of lorazepam with β-cyclodextrin. Drug Dev Ind Pharm

;19:702-12.

Vromans H, Eissens AC, Lerk CF. Mechanism of dissolution of drug-

cyclodextrin complexes. Acta Pharm Technol 1989;35:250-5.

Derle DV, Gujar KN. A critical study of analgesic, anti-pyretic and anti-

inflammatory activity of ibuprofen vs. ibuprofen and paracetamol

combination in animals. Indian Drugs 2001;7:368.

Shenoy A, Shenoy V. Antibacterial Agents, in Handbook of

Pharmaceutical Chemicals, 1st ed, Navi Mumbai: Multi-tech Publishing

Co; 2000. p. 168-9.

Khazaimia Ahereh T, Fakhreddin J. A comparison of gastrointestinal

permeability induced by diclofenac-phospolipid complex with

diclofenac acid and its sodium salts. J Pharm Sci 2003;6:352-9.

Raynolds J. Antibacterial Agents, Martindale The Extra Pharmacopoeia,

st ed, London: Royal Pharmaceutical Society; 1996. p. 272.

Higuchi T, Connors KA. Phase solubility techniques. Adv Anal Chem

Instr 1965;4:117-212.

Masson M, Sigurdardottir B, Matthiasson K, Loftsson J. Investigation

of drug-cyclodextrin complexes by a phase-distribution method:

Some theoretical and practical considerations. Chem Pharm Bull

;53:958-64.

Reddy M, Murthy T, Raju G, Muralikrishna J, Seshukumar K, Sankar D.

New spectrophotometric methods for the determination of

roxithromycin. Indian J Pharm Sci 2002;64:73-5.

Derle DV, Shinde S, Gujar KN. Inclusion complexation of roxithromycin

with β-cyclodextrin. Int J Pharm Excipient 2003;7:95-100.

Baboota S, Dhaliwal M, Kohli K. Physicochemical characterization,

in vitro dissolution behavior and pharmacodynamic studies of roficoxib-

β-cyclodextrin inclusion compounds: Preparation of roficoxib-HP-β-

cyclodextrin inclusion complex, A technical note. AAPS PharmSciTech

;6:14.

Winter C, Risley E, Nuss G. Carrageenan-induced edema in hind paw

of rats as an assay for anti-inflammatory drugs. Proc Soc Exp Bio Med

;11:544.

Derle DV, Gujar KN. Anti-inflammatory, analgesic and anti-pyretic activity

of Acorus Calamus and Curcuma Amada. Indian Drugs 2001;8:444.

Lu W, Zhang Q, Zheng L, Wang H, Li R, Zhang L. Antipyretic, analgesic

and anti-inflammatory activities of ketoprofen β-cyclodextrin inclusion

complexes in animals. Biol Pharm Bull 2004;27:1515-20.

Ulaleye S, Farombi E, Adewoye E, Owayele B, Onasanso S, Elegbe R.

Analgesic and anti-inflammatory effects of Kolaviron (A Garcina Kola

Seed Extract). Afr J Biomed Res 2000;3:171-4.

Best J, Kahn J. Research in Education, 7th ed, New Delhi: Prentice-Hall

of India Private Limited; 1999. p. 362-5.

Brown M. Introduction to thermal analysis: Techniques and applications.

New York: Chapmann and Hall; 1988. p. 121-4.

Reddy N, Ramakrishna S, Chowdary K, Diwan P. β-cyclodextrin complex

of celecoxib: Molecular modeling, characterization and dissolution

studies. AAPS PharmSciTech 2004;6:7.

Tahereh K, Fakhreddin J. A comparison of gastrointestinal permeability

induced by diclofenac-phospolipid complex with diclofenac acid and

its sodium salts. J Pharm Sci 2003;6:352-9.

McEwen J. Clinical pharmacology of piroxicam β-cyclodextrin: Implications

for innovative patient care. Clin Drug Investig 2000;19:27-31.

Dolina A, Santoyo S, Ygartua S. Influence of piroxicam: HP- β-cyclodextrin

complexation on in vitro permeation and skin retention of piroxicam.

Skin Pharmacol Appl Skin Physiol 2001;14:97-107.




DOI: http://dx.doi.org/10.22377/ajp.v2i1.167

Refbacks

  • There are currently no refbacks.